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Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence ( p  < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) ( p  < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.

Background: Data from the COVID-19 pandemic describes increases in drug use and related harms, especially fatal overdose. However, evidence is needed to better understand the pathways from pandemic-related factors to substance use behaviours. Thus, we investigated stockpiling drugs among people who use drugs (PWUD) in five cities in the United States and Canada., Methods: We used data from two waves of interviews among participants in nine prospective cohorts to estimate the prevalence and correlates of stockpiling drugs in the previous month. Longitudinal correlates were identified using bivariate and multivariate generalized linear mixed-effects modeling analyses., Results: From May 2020 to February 2021, we recruited 1873 individuals who completed 2242 interviews, of whom 217 (11.6%) reported stockpiling drugs in the last month at baseline. In the multivariate model, stockpiling drugs was significantly and positively associated with reporting being greatly impacted by COVID-19 (Adjusted Odds Ratio [AOR]= 1.21, 95% CI: 1.09-1.45), and at least daily use of methamphetamine (AOR = 4.67, 95% CI: 2.75-7.94) in the past month., Conclusions: We observed that approximately one-in-ten participants reported stocking up on drugs during the COVID-19 pandemic. This behaviour was associated with important drug-related risk factors including high-intensity methamphetamine use. While these correlations need further inquiry, it is possible that addressing the impact of COVID-19 on vulnerable PWUD could help limit drug stockpiling, which may lower rates of high-intensity stimulant use., Competing Interests: Conflicts of interest M-JM holds the Canopy Growth professorship in cannabis science at the University of British Columbia, a position established through arm’s length gifts to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia’s Ministry of Mental Health and Addictions. He has no financial relationships with the cannabis industry., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Little is known about the neuropsychiatric and neurophysiological differences that characterize abnormal recovery following a concussion. The present study aimed to investigate the psycho-affective, cognitive, and neurophysiological profiles of symptomatic, slow-to-recover, concussed athletes, asymptomatic concussed athletes, and control athletes. Seventy-eight athletes (26 symptomatic, 26 asymptomatic, 26 control) completed the Beck Depression Inventory-II, Profile of Mood States, and 2-Back task. Additionally, event-related brain potentials were recorded during an experimental three-stimulus visual Oddball paradigm. Compared to asymptomatic and control groups, the symptomatic group reported greater depression symptoms and negatively altered mood states. Symptomatic athletes also exhibited poorer cognitive performance on the 2-Back task, indicated by more errors and slower reaction time. ERP analyses indicated prolonged P3b latency for both symptomatic and asymptomatic groups, but symptomatic athletes also exhibited reduced P3b amplitude compared to both asymptomatic and control groups. For the asymptomatic group, correlations were observed between time since last concussion and functioning, but no relations were observed within the symptomatic group for any measure. The current findings provide valuable information regarding the psycho-affective, cognitive, and neurophysiological profiles of athletes with and without persistent symptoms following a concussion and highlight the need to assess and treat symptomatic, slow-to-recover athletes from a multidimensional and integrative perspective.

Background: Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking., Methods: Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site., Results: This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR., Conclusion: Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.

Objectives: Several single-tablet regimens (STRs) are now available and are recommended for first-line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been systematically studied. We examined the characteristics associated with initiation of STRs versus multi-tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV)., Methods: A retrospective cohort study of nPHIV youth aged 13-24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS (< 400 HIV-1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year., Results: Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P < 0.01). VS was associated with STR use [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01-2.58], white (AOR 2.41; 95% CI 1.13-5.13) or Hispanic (AOR 2.38; 95% CI 1.32-4.27) race/ethnicity, and baseline CD4 count 351-500 cells/μL (AOR 1.94; 95% CI 1.18-3.19) and > 500 cells/μL (AOR 1.76; 95% CI 1.0-3.10). STR use was not associated with a shorter time to VS compared with MTR use [hazard ratio (HR) 1.07; 95% CI 0.90-1.28]., Conclusions: Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV., (© 2018 British HIV Association.)

Experimental research suggests that sport-related concussion can lead to persistent alterations in children's neurophysiology and cognition. However, the search for neuropsychological tests with a similar ability to detect long-term deficits continues., Primary Objective: The current study assessed whether a target battery of neuropsychological measures of higher cognition and academic achievement would detect lingering deficits in children 2 years after injury., Research Design: Cross-sectional., Methods and Procedure: A total of 32 pre-adolescent children (16 concussion history, 16 control) completed a targeted battery of neuropsychological and academic tests., Main Outcomes and Results: Children with a history of concussion exhibited selective deficits during the Raven's Coloured Progressive Matrices, Comprehensive Trail-Making Test, and the mathematics sub-section of the WRAT-3. Deficit magnitude was significantly related to age at injury, but not time since injury., Conclusions: The current results suggest that neuropsychological measures of higher cognition and academic achievement may be sensitive to lingering deficits, and that children injured earlier in life may exhibit worse neuropsychological and academic performance.

As the HIV-infected population ages and the burden of chronic comorbidities increases, adherence to medications for HIV and diabetes and hypertension is crucial to improve outcomes. We pilot-tested a pictorial aid intervention to improve medication adherence for both HIV and common chronic conditions. Adult patients with HIV and diabetes (DM) and/or hypertension (HTN) attending a clinic for underserved patients and at risk for poor health outcomes were enrolled. Patients were randomized to receive either a pictorial aid intervention (a photographic representation of their medications, the indications, and the dosing schedule) or a standard clinic visit discharge medication list. Adherence to antiretroviral therapy (ART) for HIV and therapy for DM or HTN was compared. Predictors of ART adherence at baseline were determined using logistic regression. Medication adherence was assessed using medication possession ratio (MPR) for the 6-month interval before and after the intervention. Change in adherence by treatment group was compared by ANOVA. Among the 46 participants, there was a trend towards higher adherence to medications for HIV compared with medications for hypertension/diabetes (baseline median MPR for ART 0.92; baseline median MPR for the medication for the comorbid condition 0.79, p = 0.07). The intervention was feasible to implement and satisfaction with the intervention was high. With a small sample size, the intervention did not demonstrate significant improvement in adherence to medications for HIV or comorbid conditions. Patients with HIV are often medically complex and may have multiple barriers to medication adherence. Medication adherence is a multifaceted process and adherence promotion interventions require an approach that targets patient-specific barriers.

New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load <400 copies/mL, and CD4 + count ≥500 cells/μL, the 9-year cumulative incidence of ESRD was higher than that of their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive individuals with no comorbidities and well-controlled disease may be considered low-risk kidney donor candidates., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: The aim of the study was to examine the association between levels of past and current alcohol consumption and all-cause and liver-related mortality among people living with HIV (PLWH)., Methods: A prospective cohort study of 1855 PLWH in Baltimore, MD was carried out from 2000 to 2013. We ascertained alcohol use by (1) self-report (SR) through a computer-assisted self interview, and (2) medical record abstraction of provider-documented (PD) alcohol use. SR alcohol consumption was categorized as heavy (men: > 4 drinks/day or > 14 drinks/week; women: > 3 drinks/day or > 7 drinks/week), moderate (any alcohol consumption less than heavy), and none. We calculated the cumulative incidence of liver-related mortality and fitted adjusted cause-specific regression models to account for competing risks., Results: All-cause and liver-related mortality rates (MRs) were 43.0 and 7.2 per 1000 person-years (PY), respectively. All-cause mortality was highest among SR nondrinkers with PD recent (< 6 months) heavy drinking (MR = 85.4 deaths/1000 PY) and lowest among SR moderate drinkers with no PD history of heavy drinking (MR = 23.0 deaths/1000 PY). Compared with SR moderate drinkers with no PD history of heavy drinking, SR nondrinkers and moderate drinkers with PD recent heavy drinking had higher liver-related mortality [hazard ratio (HR) = 7.28 and 3.52, respectively]. However, SR nondrinkers and moderate drinkers with a PD drinking history of > 6 months ago showed similar rates of liver-related mortality (HR = 1.06 and 2.00, respectively)., Conclusions: Any heavy alcohol consumption was associated with all-cause mortality among HIV-infected individuals, while only recent heavy consumption was associated with liver-related mortality. Because mortality risk among nondrinkers varies substantially by drinking history, current consumption alone is insufficient to assess risk., (© 2016 British HIV Association.)

Objectives: Risk-adjusted 30-day hospital readmission rate is a commonly used benchmark for hospital quality of care and for Medicare reimbursement. Persons living with HIV (PLWH) may have high readmission rates. This study compared 30-day readmission rates by HIV status in a multi-state sample with planned subgroup comparisons by insurance and diagnostic categories., Methods: Data for all acute care, nonmilitary hospitalizations in nine states in 2011 were obtained from the Healthcare Costs and Utilization Project. The primary outcome was readmission for any cause within 30 days of hospital discharge. Factors associated with readmission were evaluated using multivariate logistic regression., Results: A total of 5 484 245 persons, including 33 556 (0.6%) PLWH, had a total of 6 441 695 index hospitalizations, including 45 382 (0.7%) among PLWH. Unadjusted readmission rates for hospitalizations of HIV-uninfected persons and PLWH were 11.2% [95% confidence interval (CI) 11.2, 11.2%] and 19.7% (95% CI 19.3, 20.0%), respectively. After adjustment for age, gender, race, insurance, and diagnostic category, HIV infection was associated with 1.50 (95% CI 1.46, 1.54) times higher odds of readmission. Predicted, adjusted readmission rates were higher for PLWH within every insurance category, including Medicaid [12.9% (95% CI 12.8, 13.0%) and 19.1% (95% CI 18.4, 19.7%) for HIV-uninfected persons and PLWH, respectively] and Medicare [13.2% (95% CI 13.1, 13.3%) and 18.0% (95% CI 17.4, 18.7%), respectively], and within every diagnostic category., Conclusions: HIV infection is associated with significantly increased readmission risk independent of demographics, insurance, and diagnostic category. The 19.7% 30-day readmission rate may serve as a preliminary benchmark for assessing quality of care of PLWH. Policy-makers may consider adjusting for HIV infection when calculating a hospital's expected readmission rate., (© 2015 British HIV Association.)

Background and Purpose: Cerebrovascular collaterals have been increasingly recognized as predictive of clinical outcomes in Moyamoya disease in Asia. The aim of this study was to characterize collaterals in North American adult patients with Moyamoya disease and to assess whether similar correlations are valid., Materials and Methods: Patients with Moyamoya disease (n = 39; mean age, 43.5 ±10.6 years) and age- and sex-matched control subjects (n = 33; mean age, 44.3 ± 12.0 years) were graded via angiography. Clinical symptoms of stroke or hemorrhage were graded separately by imaging. Correlations between collateralization and disease severity, measured by the modified Suzuki score, were evaluated in patients with Moyamoya disease by fitting a regression model with clustered ordinal multinomial responses., Results: The presence of leptomeningeal collaterals (P = .008), dilation of the anterior choroidal artery (P = .01), and the posterior communicating artery/ICA ratio (P = .004) all correlated significantly with disease severity. The presence of infarct or hemorrhage and posterior steno-occlusive disease did not correlate significantly with the modified Suzuki score (P = .1). Anterior choroidal artery changes were not specific for hemorrhage. Patients with Moyamoya disease were statistically more likely than controls to have higher posterior communicating artery/ICA ratios and a greater incidence of leptomeningeal collaterals., Conclusions: As with Moyamoya disease in Asian patients, the presence of cerebrovascular collaterals correlated with the modified Suzuki score for disease severity in North American patients with Moyamoya disease. However, anterior choroidal artery changes, which correlated with increased rates of hemorrhage in Asian studies, were not specific to hemorrhage in North Americans., (© 2014 by American Journal of Neuroradiology.)

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Background: Sensory neuropathy (SN) is common in patients with HIV. Hepatitis C (HCV) coinfection is often cited as an HIV-SN risk factor, but data to support this are lacking. This collaboration aimed to examine the association between HCV serostatus and SN risk among ambulatory HIV-positive patients., Methods: Patients with HIV were assessed in cross-sectional studies in Baltimore, Jakarta, Johannesburg, Kuala Lumpur, Melbourne, and Sydney for SN (defined by both supportive symptoms and signs). HCV seropositivity was assessed as an SN risk using a chi(2) test, followed by logistic regression modeling to correct for treatment exposures and demographics., Results: A total of 837 patients of African, Asian, and Caucasian descent were studied. HCV seroprevalence varied by site (Baltimore n = 104, 61% HCV+; Jakarta 96, 51%; Johannesburg 300, 1%; Kuala Lumpur 97, 10%; Melbourne 206, 16%; Sydney 34, 18%). HCV seropositivity was not associated with increased SN risk at any site, but was associated with reduced SN risk in Melbourne (p = 0.003). On multivariate analyses, the independent associations with SN were increasing age, height, and stavudine exposure. HCV seropositivity was not independently associated with an increased SN risk at any site, but associated independently with reduced SN risk in Baltimore (p = 0.04) and Melbourne (p = 0.06)., Conclusions: Hepatitis C (HCV) seropositivity was not associated with increased sensory neuropathy risk among HIV-positive patients at any site. While we were unable to assess HCV RNA or liver damage, the data suggest that HCV coinfection is not a major contributor to HIV-SN. HCV = hepatitis C; SN = sensory neuropathy.

Objectives: While highly active antiretroviral therapy (HAART) decreases long-term morbidity and mortality, its short-term effect on hospitalization rates is unknown. The primary objective of this study was to determine hospitalization rates over time in the year after HAART initiation for virological responders and nonresponders., Methods: Hospitalizations among 1327 HAART-naïve subjects in an urban HIV clinic in 1997-2007 were examined before and after HAART initiation. Hospitalization rates were stratified by virological responders (> or =1 log(10) decrease in HIV-1 RNA within 6 months after HAART initiation) and nonresponders. Causes were determined through International Classification of Diseases, 9th Revision (ICD-9) codes and chart review. Multivariate negative binomial regression was used to assess factors associated with hospitalization., Results: During the first 45 days after HAART initiation, the hospitalization rate of responders was similar to their pre-HAART baseline rate [75.1 vs. 78.8/100 person-years (PY)] and to the hospitalization rate of nonresponders during the first 45 days (79.4/100 PY). The hospitalization rate of responders fell significantly between 45 and 90 days after HAART initiation and reached a plateau at approximately 45/100 PY from 91 to 365 days after HAART initiation. Significant decreases were seen in hospitalizations for opportunistic and nonopportunistic infections., Conclusions: The first substantial clinical benefit from HAART may be realized by 90 days after HAART initiation; providers should keep close vigilance at least until this time.

Objective: The aim of this study was to examine Emergency Department (ED) utilization and clinical and sociodemographic correlates of ED use among HIV-infected patients., Methods: During 2003, 951 patients participated in face-to-face interviews at 14 HIV clinics in the HIV Research Network. Respondents reported the number of ED visits in the preceding 6 months. Using logistic regression, we identified factors associated with visiting the ED in the last 6 months and admission to the hospital from the ED., Results: Thirty-two per cent of respondents reported at least one ED visit in the last 6 months. In multivariate analysis, any ED use was associated with Medicaid insurance, high levels of pain (the third or fourth quartile), more than seven primary care visits in the last 6 months, current or former illicit drug use, social alcohol use and female gender. Of those who used ED services, 39% reported at least one admission to the hospital. Patients with pain in the highest quartile reported increased admission rates from the ED as did those who made six or seven primary care visits, or more than seven primary care visits vs. three or fewer., Conclusions: The likelihood of visiting the ED has not diminished since the advent of highly active antiretroviral therapy (HAART). More ED visits are to treat illnesses not related to HIV or injuries than to treat direct sequelae of HIV infection. With the growing prevalence of people living with HIV infection, the numbers of HIV-infected patients visiting the ED may increase, and ED providers need to understand potential complications produced by HIV disease.

This study was conducted to report on the technique, safety, and early efficacy of a single-incision mini-sling to treat female stress urinary incontinence (SUI). Women suffering from SUI were offered a single-incision approach to place a suburethral polypropylene mesh tape in a position similar to that of a transobturator sling without passage of needles through the groin. Retrospective data was collected on 61 patients that received the new MiniArc™ single-incision sling at a single center in the United States. Patient selection and concomitant procedures were determined by the senior authors at the center, and the senior authors were the primary surgeons in all cases. Procedures were completed under general, regional, or MAC anesthesia as determined by the surgeon. Average operative time for the sling procedure alone was short and the average blood loss was 29 cc. There were no intraoperative complications. There was one postoperative adverse event secondary to urinary retention that was resolved by loosening of the sling under local anesthesia in an office setting. The overall cure rate at 12 months determined by physician and patient assessment in 58/61 patients was 91.4%. No patients suffered pain or dyspareunia secondary to the sling, and no erosions or extrusions were reported. In this initial study, the MiniArc™ single-incision sling appears to be a safe approach to treat female SUI, and the early clinical results are encouraging.

Treatment for female stress urinary incontinence (SUI) has progressed rapidly over the past ten years in the search for less invasive methods to treat this disease. There have been over 100 procedures described in the literature to date to treat female SUI; however, only two procedures have stood the test of time and have adequate cure rates: the retropubic colposuspension (Burch, MMK) and the sling. The laparoscopic approach to minimize the Burch procedure was described in the 1990s, but the evolution of the retropubic tension-free vaginal tape sling (TVT) in the late 1990s revolutionized the treatment of female SUI. More recently, the transobturator technique (TOT) and the single-incision mini-sling have been reported in attempts to further reduce the risks of sling placement. The current chapter reviews the history of treatment of female SUI and the development of these newer, less-invasive techniques. The procedures themselves are described, the risks of mesh complications reviewed, and the literature reviewed for current data on the different approaches and procedures.

Objectives: The aim of the study was to determine the relationship between alcohol consumption and liver fibrosis as assessed by aspartate aminotransferase to platelet ratio index (APRI) in HIV-infected adults and to explore the relative contributions of alcohol and hepatitis C virus (HCV) to APRI among HIV/HCV-coinfected adults., Methods: We performed a cross-sectional analysis of data from an observational clinical cohort. Alcohol consumption was categorized according to National Institute on Alcohol Abuse and Alcoholism guidelines. We defined significant liver disease as APRI>1.5, and used multinomial logistic regression to identify correlates of increased APRI., Results: Among 1358 participants, 10.4% reported hazardous drinking. It was found that 11.6% had APRI>1.5, indicating liver fibrosis. Hazardous drinking was associated with increased APRI [adjusted relative risk ratio (RRR) 2.30; 95% confidence interval (CI) 1.26-4.17]. Other factors associated with increased APRI were male gender, viral hepatitis, and HIV transmission category of injecting drug use. Among coinfected individuals, 18.3% had APRI>1.5, and hazardous drinking was not associated with APRI. Among non-HCV-infected individuals, 5.3% had APRI>1.5 and hazardous drinking was associated with increased APRI (adjusted RRR 3.72; 95% CI 1.40-9.87)., Conclusions: Hazardous drinking is an important modifiable risk factor for liver fibrosis, particularly among non-HCV-infected patients. Clinicians and researchers must address alcohol use as the burden of liver disease increases among HIV-positive individuals.

Objectives: To define the incidence and risk factors for methicillin resistant Staphylococcus aureus (MRSA) bacteraemia in an HIV-infected population., Methods: From January 1, 2000 to December 31, 2004, we conducted a retrospective cohort study. We identified all cases of Staphylococcus aureus bacteraemia (SAB), including MRSA, among patients enrolled in the Johns Hopkins Hospital out-patient HIV clinic. A conditional logistic regression model was used to identify risk factors for MRSA bacteraemia compared with methicillin-sensitive SAB and no bacteraemia in unmatched (1:1) and matched (1:4) nested case-control analyses, respectively., Results: Of 4607 patients followed for a total of 11 020 person-years (PY) of follow-up, 216 episodes of SAB occurred (incidence: 19.6 cases per 1000 PY), including 94 cases (43.5%) which were methicillin-resistant. The incidence of MRSA bacteraemia increased from 5.3 per 1000 PY in 2000-2001 to 11.9 per 1000 PY in 2003-2004 (P=0.001). Multivariate analysis demonstrated that independent predictors of MRSA bacteraemia (vs. no bacteraemia) were injection drug use (IDU), end-stage renal disease (ESRD) and CD4 count <200 cells/microL., Conclusions: MRSA bacteraemia was an increasingly common diagnosis in our HIV-infected cohort, especially in patients with history of IDU, low CD4 cell count and ESRD.

We investigated fine-scale genetic structuring in the rare and vulnerable Mallorcan midwife toad Alytes muletensis using eight polymorphic microsatellite markers. The current range of this amphibian is restricted to some 19 sites of which six are derived from reintroductions, all located in the mountain ranges of Mallorca. We sampled tadpoles from 14 pools covering 10 natural sites and two reintroduction sites for microsatellite DNA analyses. Relatively high levels of genetic variation were found in most pools (H(E) = 0.38-0.71, allelic richness = 2.6-6.2). Only at one pool has the population recently gone through a bottleneck. Dispersal between pools in different torrents does not occur whereas downstream dispersal between pools within the same torrent does happen at low frequencies. This occasional exchange of individuals does not lead to neighbouring pools in the same torrent being panmictic. This can be concluded because all F(ST) values (0.12-0.53) differ significantly from zero and STRUCTURE analyses identified neighbouring pools as separate populations. Furthermore, assignment and migration tests showed little exchange between neighbouring pools. If upstream locations or complete torrents go extinct, they are unlikely to be recolonized naturally. For conservation purposes, reintroductions of tadpoles to sites where local extinctions have occurred may therefore be advisable.

Objectives: Alterations in body shape and composition are associated with HIV/AIDS. Wasting remains prevalent; increasingly, lipodystrophy is reported. Obesity is also epidemic in the USA. In this study, we sought to characterize the body changes reported by women attending a US urban clinic, and to evaluate contributing factors using inexpensive methods that are readily available in clinical practice., Methods: In an urban Maryland clinic, a cross-section of HIV-infected women were evaluated by self report, anthropomorphic measurements, bioelectric impedance analysis (BIA) and chart review; they were categorized as no change, lipodystrophy, weight loss/wasting or weight gain/obesity., Results: One hundred and sixty-one women were evaluated: 144 (89%) were African-American; 100 (62%) had used intravenous drugs and 40 (25%) were actively injecting drugs, while 39 (24%) smoked crack. Ninety-five (59%) were on highly active antiretroviral therapy (HAART) for a median period of 11.7 months [interquartile range (IQR)=4.5-24.2]. Since starting current HAART or in the previous year, 12 (7.4%) reported lipodystrophy changes, 85 (52.8%) weight gain, 27 (16.8%) overall weight loss, and 37 (23.0%) no change. Lipodystrophy was associated with higher CD4 percentage (P=0.03), lower frequency of crack use (P=0.04) and higher educational level (P=0.03). Weight loss correlated with longer duration of infection (P=0.01), select BIA results and increased rate of crack use (P=0.005). Weight gain was associated with higher fat mass (P=0.005), higher peak viral load (P=0.02), and lower rate of intravenous drug use (P=0.03)., Conclusions: Self-reported changes in body shape were common. Obesity and complications of illicit drug use were more prevalent than lipodystrophy in this inner-city population of HIV-positive women.

Objectives: To study the relationship between exposure to protease inhibitor (PI) therapy and increased risk of cardiovascular events in HIV-infected patients., Methods: We estimated the risk of cardiovascular disease (CVD) events with PI exposure in a cohort of HIV-infected patients using a time-dependent Cox proportional hazards model adjusting for the major CVD risk factors. Only the first CVD event for each subject was counted., Results: Of a total of 7542 patients, 77% were exposed to PIs. CVD event rates were 9.8/1000 and 6.5/1000 person-years of follow-up (PYFU) in the PI-exposed and nonexposed groups, respectively (P=0.0008). PI exposure >/=60 days was associated with an increased risk of CVD event [adjusted hazards ratio (HR(adj)) 1.71; 95% confidence interval (CI) 1.08-2.74; P=0.03]. Results from a subgroup of patients aged between 35 and 65 years were similar (HR(adj) 1.90; 95% CI 1.13-3.20; P=0.02). Other significant risk factors included smoking status, age, hypertension, diabetes mellitus and pre-existing CVD., Conclusions: Patients exposed to PI therapy had an increased risk of CVD events. Clinicians should evaluate the risk of CVD when making treatment decisions for HIV-infected patients.

Objective: To determine if HIV-1 RNA and CD4 lymphocyte thresholds for the initiation of highly active antiretroviral therapy (HAART) are associated with clinical response to therapy., Design: Observational cohort study., Setting: Johns Hopkins Hospital HIV Clinic., Patients: HIV-infected adults., Intervention: Patients initiating HAART (n = 530) were compared with concurrent patients who did not receive HAART (n = 484)., Main Outcome Measure: Progression to a new AIDS-defining illness or death., Results: The average duration of follow-up for the cohort was 22 months. HAART resulted in decreased disease progression among persons with fewer than, but not more than, 200 x 10(6) CD4 lymphocytes/l prior to treatment. Among persons receiving HAART, plasma HIV-1 RNA level prior to therapy was not associated with HIV disease progression within CD4 T-lymphocyte count strata. In a Cox multivariate proportional hazards model that adjusted for age, sex, race, prior opportunistic infection, and CD4 T lymphocytes, < or = 200 x 10(6) CD4 lymphocytes/l was the strongest predictor of disease progression. HIV-1 RNA level prior to starting HAART of < 5000 copies/ml, 5001-55 000 copies/ml, or > 55 000 copies/ml was not associated with disease progression on therapy, particularly among persons with > 200 x 10(6) CD4 lymphocytes/l. There was no sex difference in disease progression on treatment., Conclusions: Our data suggest that current guidelines for initiating HAART should place greater emphasis on CD4 lymphocyte than HIV-1 RNA level for both men and women. Further longitudinal follow-up will be needed to better ascertain whether HAART initiated at > 200 x 10(6) CD4 lymphocytes/l is effective in slowing disease progression.

Objective: To compare the effectiveness of initial highly active antiretroviral therapy with either: a single protease inhibitor (PI); ritonavir (RTV)/saquinavir (SQV); or efavirenz (EFV) plus nucleoside reverse transcriptase inhibitors., Design: Cohort study., Setting: Urban HIV clinic., Patients: Five-hundred and forty-five HIV-1-infected individuals with minimal antiretroviral exposure who started combination therapy with > or = 3 antiretroviral drugs and > or = 1 NRTI to which they had not previously been exposed (single PI, 416; RTV/SQV, 68; EFV, 61)., Main Outcome Measures: HIV-1 RNA < 400 copies/ml within 8 months of starting therapy; time to HIV-1 RNA rebound to > 1000 copies/ml in the subset of patients achieving initial viral suppression; change in CD4 cell count from baseline within 12 months of starting therapy., Results: By intent-to-treat analysis, initial viral suppression was achieved by 72% of patients in the EFV group, compared to 49% in the single PI group (P = 0.001) and 51% in the RTV/SQV group (P = 0.019). Among patients who achieved initial viral suppression, time to viral rebound was similar in the three groups. Durable viral suppression (> or = 3 consecutive HIV-1 RNA levels < 400 copies/ml for > 6 months) was achieved by 53% of patients in the EFV group, 26% in the single PI group, and 29% in the RTV/SQV group (P < 0.05 for both comparisons with EFV). The median CD4 cell count increase was 139 x 10(6) cells/l, and was similar in the three groups., Conclusions: In agreement with a recent clinical trial, use of initial EFV-based combination antiretroviral therapy was associated with higher rates of viral suppression than PI-based therapy in a clinical cohort.

Technologic advances in delivery systems and imaging have allowed expansion of endovascular surgery indications to include the treatment of thoracic aortic disease. Delayed exclusion of traumatic proximal aortic disruption has been shown to be technically feasible, with a low risk of false aneurysm rupture. Long-term endovascular exclusion of these lesions may be precluded by the short or poor quality neck available below the origin of the left subclavian artery for graft fixation. A case report of a traumatic aortic disruption treated with staged subclavian-to-carotid transposition and subsequent endograft fixation is presented. The uncovered bare wire portion of the stent was placed across the left carotid artery. One-year follow-up demonstrated complete exclusion of the false aneurysm, with stable graft fixation, and no neurologic deficits. This technique may provide a means whereby proximal aortic pathology is safely excluded without regard to the length or quality of juxtasubclavian neck available for fixation.

Study Objective: To evaluate the effectiveness of laparoscopic Burch colposuspension in the treatment of recurrent stress urinary incontinence in women with previous vaginal or abdominal retropubic continence surgery., Design: Retrospective analysis over 36 months (Canadian Task Force classification III)., Setting: Community hospital., Patients: Thirty-three consecutive patients., Intervention: Laparoscopic Burch colposuspension., Measurements and Main Results: Data were obtained by retrospective chart review, telephone interviews, and follow-up physical examinations. Of the 33 patients, 17 (52%) had undergone open retropubic procedures (Burch or Marshall-Marchetti-Krantz), 11 (33%) had had vaginal retropubic needle suspension, and 5 (15%) pubovaginal sling operation. Additional laparoscopic and/or vaginal reconstructive surgery was completed in 32 women (97%) at time of laparoscopic Burch. Average overall operating time was 165 minutes (range 60-287 min), mean estimated blood loss was 178 ml (range 50-600 ml), and hospital stay was 1.1 days. Three intraoperative complications occurred, two cystotomies and one serosal bowel injury. Postoperative objective evaluation over average follow-up of 18.6 months revealed a 90% stress urinary incontinence cure rate., Conclusion: Laparoscopic Burch colposuspension is safe and effective treatment of recurrent stress urinary incontinence in women who have undergone previous procedures for retropubic continence.

The present review focuses on the most recently published English language literature, and addresses results and complications associated with the laparoscopic approach to urinary incontinence, anterior vaginal wall prolapse, and lower urinary tract injury. Laparoscopic Burch procedures continue to show equal efficacy, but lower morbidity as compared with conventional open techniques. Lower urinary tract injuries may also be managed effectively using the same techniques as those employed in open procedures. Laparoscopy continues to be considered a mode of surgical access, and is effective in treating urinary incontinence, anterior vaginal wall prolapse, and lower urinary tract injuries.

Objective: To identify the effects of substance abuse status (active, former, and never) on utilization of highly active antiretroviral therapy (HAART), medication adherence, and virologic and immunologic responses to therapy., Design: Prospective cohort study of 764 HIV-1-infected patients who attended an urban HIV clinic and participated in a standardized interview., Main Outcome Measures: Past utilization of HAART, self-reported nonadherence with antiretroviral therapy, and changes in HIV-1 RNA level and CD4+ lymphocyte count relative to prior peak and nadir, respectively., Results: Forty-four percent of active drug users failed to utilize HAART compared with 22% of former drug users and 18% of non-drug users (p <.001 for both comparisons). Among participants who were taking antiretroviral therapy when interviewed, active drug users were more likely to report medication nonadherence (34% vs. 24% of nonusers and 17% of former users), had a smaller median reduction in HIV-1 RNA from baseline (0.8 log10 copies/ml vs. 1.7 in nonusers and 1.6 in former users), and had smaller median increases in CD4+ lymphocyte count from baseline (65 cells/mm3 vs. 116 in nonusers and 122 in former users) (p <.05 for all comparisons with active users)., Conclusions: Active drug use was strongly associated with underutilization of HAART, nonadherence, and inferior virologic and immunologic responses to therapy, whereas former drug users and non-drug users were similar in all outcomes. Effective strategies are needed that integrate HIV-1 and substance abuse treatments.

Background: The advent of highly active antiretroviral therapy (HAART) has reduced the incidence of most AIDS-related opportunistic illnesses (OI) and death in HIV-infected individuals. We investigated whether there are demographic disparities in HIV disease progression in the HAART era compared with before., Methods: HIV-infected patients in an urban HIV clinical practice in the USA were compared using survival methods for time to a new AIDS-defining OI or death in therapeutic era 1 (monotherapy and combination therapy; 1990--1995; n = 2016) versus era 2 (HAART; 1996--1999; n = 2165)., Results: A total of 1037 (51.4%) events occurred in era 1; 666 (30.8%) events occurred in era 2. In women, the median disease-free survival time increased by 14% (CD4 cell counts > 200 cells/mm(3) at baseline) and 34% (CD4 cell counts < or = 200) in era 2 compared with era 1, whereas for men it increased by 43 and 100%. The relative hazard (RH) of progression for women compared with men in era 2 compared with era 1 was 1.34. For injecting drug use (IDU), disease-free survival time increased by 16% and 34% in era 2 compared with era 1, whereas non-IDU improved by 65 and 135%. The RH of progression for IDU compared with non-IDU in era 2 compared with era 1 was 1.39. No significant differences were detected by race or other HIV transmission risk group., Conclusion: Disease-free survival time was extended with the use of HAART, but these gains were not equally distributed by sex and IDU in our cohort.

Objective: Previous studies have shown a decrease in hospitalization rates associated with the introduction of highly active antiretroviral therapy (HAART). To evaluate hospitalization rates and patterns in discharge diagnoses that changed between 1995 and 1998 and to examine risk factors for hospitalization in HIV-positive patients, we conducted a cohort study., Patients and Methods: All inpatient hospitalizations of 2,151 HIV-positive patients enrolled in our university-based HIV clinic between January 1, 1994 and December 31, 1998 with a CD4 count within a 6-month calendar semester were examined to evaluate hospitalization rates, discharge diagnoses, and intensive care department use. Negative binomial regression was used to assess the effect of various risk factors on hospitalization., Results: Hospitalization rates decreased between 1995 and 1996 but increased between 1997 and 1998. In multivariate regression, female gender (incidence rate ratio [IRR], 1.45; p <.001), injection drug use (IRR, 1.36; p <.001), and having received no antiretroviral therapy were strong predictors of total hospitalization. White race, low CD4 count, and no antiretroviral treatment were strong predictors of hospitalization for an opportunistic infection. Female gender (IRR, 1.45; p <.001), African-American ethnicity (IRR, 1.22, p =.05), no antiretroviral treatment, and low CD4 counts were predictive of higher hospitalization rates for nonopportunistic infection-related diagnoses. Intensive care department-use was associated with white ethnicity (IRR, 1.86; p =.028), heterosexual transmission of HIV (IRR, 1.90; p =.009), no antiretroviral treatment, and low CD4 count at enrollment., Conclusions: Our data indicate that hospitalization rates decreased between 1995 and 1997 after introduction of HAART, but that they then increased between 1997 and 1998, particularly for diagnosed nonopportunistic infections. If these trends continue, it indicates that patients may be developing previously unseen comorbidities and that HAART may have reached or exceeded a threshold in its effectiveness in reducing the clinical morbidity that results in hospital admission.

Purpose: To determine the effect of several interventions on adherence to tuberculosis preventive therapy., Methods: We conducted a randomized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis. Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly (Supervised group, n = 99), daily self-administered isoniazid with peer counseling and education (Peer group, n = 101), or routine care (Routine group, n = 100). Patients within each arm were also randomly assigned to receive an immediate or deferred monthly $10 stipend for maintaining adherence. The endpoints of the trial were completing 6 months of treatment, pill-taking as measured by self-report or observation, isoniazid metabolites present in urine, and bottle opening as determined by electronic monitors in a subset of patients., Results: Completion of therapy was 80% for patients in the Supervised group, 78% in the Peer group, and 79% in the Routine group (P = 0.70). Completion was 83% (125 of 150) among patients receiving immediate incentives versus 75% (112 of 150) among patients with deferred incentives (P = 0.09). The proportion of patients who were observed or reported taking at least 80% of their doses was 82% for the Supervised arm of the study, compared with 71% for the Peer arm and 90% for the Routine arm. The proportion of patients who took 100% of doses was 77% for the Supervised arm (by observation), 6% for the Peer arm (by report), and 10% for the Routine arm (by report; P <0.001). Direct observation showed the median proportion of doses taken by the Supervised group was 100%, while electronic monitoring in a subset of patients showed the Peer group (n = 27) took 57% of prescribed doses and the Routine group (n = 32) took 49% (P <0.001). Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold standard. There were no significant differences in electronically monitored adherence by type of incentive., Conclusion: Adherence to isoniazid preventive therapy by injection drug users is best with supervised care. Peer counseling improves adherence over routine care, as measured by electronic monitoring of pill caps, and patients receiving peer counseling more accurately reported their adherence. More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups.

Background: Pancreatitis is a known adverse effect of the nucleoside reverse transcriptase inhibitors, particularly didanosine. Hydroxyurea has been used to potentiate the antiviral efficacy of didanosine, but recently there has been concern that severe and even fatal pancreatitis may be more likely to occur when hydroxyurea is used in combination with didanosine. We investigated the incidence of pancreatitis in patients using nucleoside analogues with or without hydroxyurea., Methods: Data were obtained from patients followed longitudinally on the Johns Hopkins HIV Clinic. Incidence rates of pancreatitis were calculated for each antiretroviral regimen that included zidovudine, stavudine, didanosine (+ hydroxyurea), and didanosine + stavudine (+ hydroxyurea). Poisson regression was used to compare the relative rate of pancreatitis for each regimen adjusting for other covariates., Results: A total of 2613 patients received at least one of the nucleoside reverse transcriptase inhibitor-containing regimens. There were 33 cases of pancreatitis. The crude incidence rate of pancreatitis ranged from 0.18 cases per 100 person-years on therapy for zidovudine to 6.25 cases per 100 person-years for didanosine + hydroxyurea. Compared to didanosine alone, and adjusting for CD4 cell count and other variables, the relative risk (RR) of pancreatitis was 8.56 [95% confidence interval) CI, 1.85-35.59] for didanosine + hydroxyurea, and 2.35 (95% CI, 0.46-11.89) for didanosine + stavudine + hydroxyurea. For any use of hydroxyurea, the RR = 4.01 (95% CI, 1.02-15.89). Other risk factors for pancreatitis included a CD4 cell count < 200 x 106 cells/l, female sex, and a history of pancreatitis., Conclusions: Our data show that the risk of pancreatitis is four-fold higher when hydroxyurea is used. The use of hydroxyurea with didanosine should probably be discouraged if other treatment options are available.

The present study examined predictors of participation and retention for patients treated at an urban, hospital-based outpatient substance abuse treatment clinic. All patients were interviewed using the Addiction Severity Index (ASI) at the time of admission. Based on lifetime diagnostic history of psychoactive substance abuse/dependence, patients (N=268) were classified as: alcohol-only, drug(s)-only, and alcohol+drug(s). Alcohol-only patients were significantly older, more likely to be Caucasian, married, have less than a high school education, and be employed than drug-only or alcohol/drug patients. Using multiple regression analysis, substance use status did not predict treatment participation and retention, whereas race, gender and employment composite score were significant predictors. Specifically, patients attended more sessions and remained in treatment longer if they were Caucasian, male and had a high employment composite score. These findings suggest that type of substance abuse may be overemphasized as a predictor of outpatient drug-free treatment retention, and that greater emphasis should be placed on tailoring treatment to patients' cultural, gender and vocational needs.

Vaginal evisceration following colpocleisis is a very rare event and, to our knowledge, there has only been one previous case report. An 86-year-old woman presented to the Emergency Department with acute onset of abdominal pain occurring following a bowel movement. Six months previously, she had undergone a colpocleisis for recurrent vaginal vault prolapse. On presentation to the emergency room, she was noted to have 60 cm of necrotic small bowel protruding through her vaginal introitus. She was taken to the operating room for resection of the small bowel and closure of her colpocleisis. The closure of the vaginal defect was difficult and required a vaginal approach employing an allogenic dermal graft. This was accomplished and the patient had an uneventful recovery and was discharged home. At 18 months followup, she has had no complication or recurrence. Evisceration following colpocleisis is a rare event, but can be very difficult to manage and we suggest consideration of employing a graft to reinforce the repair.

Study Objective: To estimate the rate of injury to the lower urinary tract during laparoscopic Burch urethropexy and/or paravaginal repair., Design: Retrospective analysis over 30 consecutive months (Canadian Task Force classification II-2). Setting. Community hospital., Patients: One hundred seventy-one consecutive patients., Intervention: Laparoscopic Burch urethropexy and/or paravaginal repair., Measurements and Main Results: All patients had intraoperative transurethral videocystoscopy performed with intravenous injection of indigo carmine dye to assess potential injury to bladder or ureter. Four women (2.3%, CI -0.71-0.03) had injury to the lower urinary tract. All four injuries were cystotomies, two in women with previous open retropubic urethropexy. No ureteral ligation or intravesical placement of suture was diagnosed., Conclusion: Despite most patients having both Burch urethropexy and paravaginal repair, the lower urinary tract injury rate of 2.3% is much lower than the reported 10% for patients having Burch urethropexy alone performed by laparotomy. Reported benefits of laparoscopy including less blood loss and better visualization may explain this result.

Data derived from studies conducted before 1996 consistently showed that anemia was a common occurrence in patients with human immunodeficiency (HIV) Infection and an Independent risk factor for early death. Correction of anemia was associated with reversal of this increased risk. Highly active antiretroviral therapy (HAART) has been shown to reduce HIV disease progression and mortality. In the HAART era, HIV-related anemia is still common and independently associated with decreased survival, with a decreased risk of mortality associated with recovery from anemia. Epoetin alfa treatment has been shown to correct anemia and significantly improve quality of life (QOL) in patients with HIV disease. Additional data on the effect of correction of anemia with epoetin alfa treatment on survival in patients with HIV infection are needed.

To illustrate the importance of adjusting the estimates of cumulative incidence of acquired immunodeficiency syndrome (AIDS) related illnesses for competing risk of other causes of death, we compared unadjusted and adjusted (for competing events) incidence estimates for four AIDS illnesses: pneumocystis cavinii pneumonia (PCP), mycobacterium avium complex (MAC), cytomegalovirus (CMV), and esophageal candidiases. The study population was patients followed by the Johns Hopkins Hospital AIDS Service between 1989 to 1995. Ratios of 4 year unadjusted incidence estimates to 4 year adjusted incidence estimates for the four diseases ranged from 1.38 to 1.86, corresponding to cumulative death rates of 61% to 69%. For CMV, the ratios of 4 year unadjusted to adjusted incidence estimates for five groups of patients ranged from 1.5 to 2.33, corresponding to cumulative death rates of 48% to 78%. We conclude that ignoring the competing risk of death can result in substantial overestimation of disease occurrence, which may give misleading results in estimating and comparing the occurrence of a disease of interest.

To determine the relationship of combination antiretroviral therapy and bacterial pneumonia, we assessed incidence of and risk factors for bacterial pneumonia in 1,898 human immunodeficiency virus (HIV)-infected patients with CD4 cell counts < 200/mm(3) followed in the Johns Hopkins HIV clinic between 1993 and 1998. A total of 352 episodes of bacterial pneumonia occurred during 2,310 patient-years of follow-up. Incidence of bacterial pneumonia decreased from 22.7 episodes/100 person-years (py) in the first half of 1993 to 12.3 episodes/100 py in the first half of 1996, reaching a nadir of 9.1 episodes/100 py in the second half of 1997 (p < 0.05). The use of protease inhibitor-containing regimens was associated with a decreased risk of bacterial pneumonia (risk ratio [RR] 0.55, 95% CI 0.31 to 0.94). Lower CD4 cell counts (RR 2.22, 95% CI 1.54 to 3.18), injection drug use as HIV transmission category (RR2.0, 95% CI 1.43 to 2.76), and prior Pneumocystis carinii pneumonia (RR 3.88, 95% CI 1.65 to 9.16) were also significantly associated with bacterial pneumonia. Trimethoprim-sulfamethoxazole and macrolide use were not significantly associated with risk of bacterial pneumonia. There has been a dramatic decline in the incidence of bacterial pneumonia resulting from the use of combination antiretroviral therapy containing protease inhibitors.

The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) demonstrated the efficacy of hydroxyurea in reducing the rate of painful crises compared to placebo. We used resource utilization data collected in the MSH to determine the cost-effectiveness of hydroxyurea. The MSH was a randomized, placebo-controlled double-blind clinical trial involving 299 patients at 21 sites. The primary outcome, visit to a medical facility, was one of the criteria to define occurrence of painful crisis. Cost estimates were applied to all outpatient and emergency department visits and inpatient hospital stays that were classified as a crisis. Other resources for which cost estimates were applied included hospitalization for chest syndrome, analgesics received, hydroxyurea dosing, laboratory testing, and clinic visits for management of patient care. Annualized differential costs were calculated between hydroxyurea- and placebo-receiving patients. Hospitalization for painful crisis accounted for the majority of costs in both arms of the study, with an annual mean of $12,160 (95% CI: $9,440, $14,880) for hydroxyurea and $17,290 (95% CI: $13,010, $21,570) for placebo. The difference in means was $5,130 (95% CI: $60, $10,200; P = 0.048). Chest syndrome was the next largest cost with a mean difference of $830 (95% CI: $-340, $2,000; P = 0.16). The hydroxyurea arm was also associated with lower costs for emergency department visits, transfusion, and use of opiate analgesics. In total, the annual average cost per patient receiving hydroxyurea was $16,810 (95% CI: $13,350, $20,270) and the annual average costs per patient receiving placebo was $22,020 (95% CI: $17,340, $26,710). The difference in means was $5,210 (95% CI: $-610, $11,030; P = 0.21). The cost of hydroxyurea with the more intensive monitoring required when using this drug appears to be more than offset by decreased costs for medical care of painful crisis and analgesic use. Although the total cost difference was not significant statistically, these results suggest that hydroxyurea therapy is cost-effective compared to placebo in the management of adult patients with sickle cell anemia. If hydroxyurea can prevent development of chronic organ damage, long-term savings may be even greater.

Since 1997, expert panel guidelines for HIV care have recommended the use of combination antiretroviral therapy with at least 3 antiretroviral drugs. Several studies have examined the cost effectiveness of 3-drug combination antiretroviral regimens for the treatment of HIV infection. Analyses comparing a 3-drug protease inhibitor-containing regimen with a 1- or 2-drug non-nucleoside reverse transcriptase inhibitor regimen have consistently yielded incremental direct cost estimates ranging from $US10,000 to just over $US13,000 per year of life saved. In Western societies, such an incremental cost per year of life saved compares favourably with chronic therapy for other diseases and argues for the adoption of these drugs by payors and policy makers. The reason for this favourable cost-effectiveness ratio appears to be the decrease in opportunistic complications and hospitalisation associated with the effective use of combination antiretroviral therapy. Whether this initial benefit will be maintained is not yet known. Other comorbid illnesses such as hepatitis C or renal failure may subsequently increase the cost of HIV care, and some analyses suggest that resistance may develop to these drugs over the long term. In addition, studies are needed to assess the cost effectiveness of these therapies in developing countries where the expense of these drugs appears to put them out of reach. The collection and analysis of economic data will continue to be needed as newer HIV therapies become available and the HIV healthcare environment evolves. Quantifying medical care costs and calculating cost effectiveness involve assessing a moving target. Economic analyses of HIV infection must evolve in tandem with therapeutic changes to continue to be relevant to policy makers, payors of care, and those who provide and receive HIV care.

Background: Sensory neuropathy is a common adverse effect of the nucleoside analogue anti-retroviral drugs didanosine (ddl) and stauvudine (d4T). These drugs are increasingly being used in combination, and it is not currently known whether the incidence of neuropathy is higher with combination compared to individual drug use. It is also not known if hydroxyurea, used to potentiate the antiviral efficacy of these drugs, may also increase the risk of neuropathy. The purpose of this analysis is to investigate if the combination of ddl and d4T, with or without hydroxyurea, has a higher incidence of neuropathy than a single drug regimen., Methods: Data were obtained from patients followed longitudinally by the Johns Hopkins AIDS Services. Incidence rates of development of neuropathy were calculated for each of five regimens: ddl (+/- hydroxyurea), ddl + d4T (+/- hydroxyurea), and d4T. Cox proportional hazard regression was used to compare the relative risk of neuropathy for each regimen adjusting for CD4 cell count, other drugs received, and time on therapy., Results: A total of 1116 patients received at least one of the five regimens. There were 117 cases of neuropathy. The crude incidence rate of neuropathy ranged from 6.8 cases per 100 person-years for ddl to 28.6 cases per 100 person-years for ddl + d4T + hydroxyurea. Compared with ddl alone, and adjusting for CD4 cell counts and other variables, the relative risk of neuropathy was 1.39 [95% confidence interval (CI): 0.84-2.32] for d4T alone, 2.35 (95% CI: 0.69-8.07) for ddl + hydroxyurea, 3.50 (95% CI: 1.81-6.77) for ddl + d4T, and 7.80 (95% CI: 3.92-15.5) for ddl + d4T + hydroxyurea., Conclusions: Based on the data, the risk of neuropathy is additive or even synergistic for ddl + d4T + hydroxyurea compared with ddl or d4T alone. The combination of ddl + d4T also increases the risk of neuropathy but less than when hydroxyurea is included.

Context: Use of antiretroviral drugs, including protease inhibitors, for treatment of human immunodeficiency virus (HIV) infection has been anecdotally associated with hepatotoxicity, particularly in persons coinfected with hepatitis C or B virus., Objectives: To ascertain if incidence of severe hepatotoxicity during antiretroviral therapy is similar for all antiretroviral drug combinations, and to define the role of chronic viral hepatitis in its development., Design: Prospective cohort study., Setting: University-based urban HIV clinic., Patients: A total of 298 patients who were prescribed new antiretroviral therapies between January 1996 and January 1998, 211 (71%) of whom received protease inhibitors as part of combination therapy (median follow-up, 182 days) and 87 (29%) of whom received dual nucleoside analog regimens (median follow-up, 167 days). Chronic hepatitis C and B virus infection was present in 154 (52%) and 8 (2.7%) patients, respectively., Main Outcome Measure: Severe hepatotoxicity, defined as a grade 3 or 4 change in levels of serum alanine aminotransferase and aspartate aminotransferase, evaluated before and during therapy., Results: Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients (95% confidence interval [CI], 7.2%-14.4%). Ritonavir use was associated with a higher incidence of toxicity (30%; 95% CI, 17.9% -44.6%). However, no significant difference was detected in hepatotoxicity incidence in other treatment groups, ie, nucleoside analogs (5.7%; 95% CI, 1.2%-12.9%), nelfinavir (5.9%; 95% CI, 1.2%-16.2%), saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir(6.8%; 95% CI, 3.0%-13.1 %). Although chronicviral hepatitis was associated with an increased risk of severe hepatotoxicity among patients prescribed nonritonavir regimens (relative risk, 3.7; 95% CI, 1.0-11.8), most patients with chronic hepatitis C or B virus infection (88%) did not experience significant toxic effects. Rate of severe toxicity with use of any protease inhibitor in patients with hepatitis C infection was 12.2% (13/107; 95% CI, 6.6%-19.9%). In multivariate logistic regression, only ritonavir (adjusted odds ratio [AOR], 8.6; 95% CI, 3.0-24.6) and a CD4 cell count increase of more than 0.05 x 10(9)/L (AOR, 3.6; 95% CI, 1.0-12.9) were associated with severe hepatotoxicity. No irreversible outcomes were seen in patients with severe hepatotoxicity., Conclusions: Our data indicate that use of ritonavir may increase risk of severe hepatotoxicity. Although hepatotoxicity may be more common in persons with chronic viral hepatitis, these data do not support withholding protease inhibitor therapy from persons coinfected with hepatitis B or C virus.

Complications of laparoscopic procedures occur in up to 10% of cases. The most lethal complication relates to injury of major retroperitoneal vascular structures. A case of aortoenteric fistula referred to the vascular surgical service 1 month following emergency repair of laparoscopic aortic injury is presented. A technique utilizing a saphenous vein panel graft for distal aortic repair is described. Review of reported cases demonstrates that major retroperitoneal vascular injury during laparoscopy is rare, with a reported incidence of 3 to 10/10,000 procedures, and a mortality of up to 20%. Simple suture repair is the usual form of treatment, but specialized techniques are occasionally required.

Objectives: To report a case of acute chest syndrome (ACS) of sickle cell disease treated successfully with nitric oxide and to review the physiologic effects of nitric oxide and its potential ability to improve outcome in ACS., Design: Descriptive case report., Setting: Eighteen-bed pediatric intensive care unit in a university children's hospital., Patient: A 15-yr-old black male with sickle cell disease, bilateral pulmonary infiltrates, refractory hypoxemia, and unstable hemodynamics., Intervention: In addition to exchange transfusion, invasive hemodynamic monitoring, and aggressive ventilatory support, inhaled nitric oxide was administered in the gas mixture in a concentration of 20 ppm for 72 hrs., Measurements and Main Results: Cardiac output, pulmonary arterial pressure, pulmonary artery occlusion pressure, systemic vascular resistance, pulmonary vascular resistance, shunt fraction, and alveolar-arterial oxygen gradient were compared with and without inhaled nitric oxide. Marked reductions in pulmonary arterial pressure and pulmonary vascular resistance were noted. Cardiac output improved, and shunt fraction and alveolar-arterial oxygen gradient were markedly reduced. The patient required decreased ventilator and hemodynamic support and rapidly made a complete recovery., Conclusions: Nitric oxide may be beneficial for patients with ACS because of its ability to ameliorate pulmonary hypertension and ventilation/perfusion mismatch. Nitric oxide may confer some protection against polymerization of sickle hemoglobin and exert a reversible antiplatelet effect that may be beneficial in ACS. Further study is necessary to determine the safety and efficacy of inhaled nitric oxide as a treatment for ACS.

Background: The use of protease inhibitor-containing (PI) combination antiretroviral therapy has led to a reduction in the incidence of opportunistic illness and mortality (events) in HIV infection. We wished to quantify the changing incidence of these events in our clinical practice and delineate the relationship between CD4, HIV-1 RNA, and development of events in patients receiving PI combination therapy., Methods: We assessed HIV-infected patients with CD4 counts < or =500 cells x10(6)/l. We calculated the incidence of events from 1994 through 1998 and analyzed the association of temporal changes in event incidence and use of antiretroviral therapy. In patients on PI combination therapy, we determined the probability of achieving and maintaining an undetectable HIV-1 RNA response and determined the association of CD4, HIV-1 RNA, and developing an event., Results: The incidence of opportunistic illness declined from 23.7 events/100 person-years in 1994 to 14.0 events/100 person-years in 1998 (P<0.001). Mortality declined from 20.2 deaths/100 person-years in 1994 to 8.4 deaths/ 100 person-years in 1998 (P<0.001). Use of PI combination therapy was associated with a relative rate of opportunistic illness or death of 0.66 [95% confidence interval (CI), 0.51-0.85; P<0.001]. The relative incidence of each of 16 opportunistic illnesses was approximately the same in 1998 as in 1994 except for lymphoma, cervical cancer and wasting syndrome which do not appeared to have declined in incidence. Approximately 60% of patients who received PI therapy achieved an undetectable HIV-1 RNA, and 65% of these patients maintained durable suppression of HIV-1 RNA. Achieving an undetectable HIV-1 RNA was associated with a decreased risk of an event, and was the variable most strongly associated with an increase in CD4 level. By multivariate analysis, the concurrent CD4 level was most strongly associated with developing an event., Conclusions: We observed a significant decline in the incidence of opportunistic illness and death from 1994 through 1998 associated with combination antiretroviral therapy. Patients who develop events while being treated with PI combination therapy were not likely to have achieved an undetectable HIV-1 RNA and are likely to have a low concurrent CD4 level.